A Unified Linear Viscoelastic Model of the Cell Nucleus Defines the Mechanical Contributions of Lamins and Chromatin.
nuclear lamins
nucleus mechanics
nucleus mechanobiology
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
21
05
2019
revised:
22
01
2020
entrez:
25
4
2020
pubmed:
25
4
2020
medline:
25
4
2020
Statut:
epublish
Résumé
The cell nucleus is constantly subjected to externally applied forces. During metazoan evolution, the nucleus has been optimized to allow physical deformability while protecting the genome under load. Aberrant nucleus mechanics can alter cell migration across narrow spaces in cancer metastasis and immune response and disrupt nucleus mechanosensitivity. Uncovering the mechanical roles of lamins and chromatin is imperative for understanding the implications of physiological forces on cells and nuclei. Lamin-knockout and -rescue fibroblasts and probed nucleus response to physiologically relevant stresses are generated. A minimal viscoelastic model is presented that captures dynamic resistance across different cell types, lamin composition, phosphorylation states, and chromatin condensation. The model is conserved at low and high loading and is validated by micropipette aspiration and nanoindentation rheology. A time scale emerges that separates between dominantly elastic and dominantly viscous regimes. While lamin-A and lamin-B1 contribute to nucleus stiffness, viscosity is specified mostly by lamin-A. Elastic and viscous association of lamin-B1 and lamin-A is supported by transcriptional and proteomic profiling analyses. Chromatin decondensation quantified by electron microscopy softens the nucleus unless lamin-A is expressed. A mechanical framework is provided for assessing nucleus response to applied forces in health and disease.
Identifiants
pubmed: 32328409
doi: 10.1002/advs.201901222
pii: ADVS1598
pmc: PMC7175345
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1901222Informations de copyright
© 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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